How Does DNA Work?
At its core, DNA is a like recipe book with the ingredients and methods required to make your entire body. But how the devil does it work?
What is DNA?
The DNA double helix is a beautiful molecule, evolved over billions of years to create the diversity of all life on Earth.
DNA is a self-replicating molecule made up of four nucleotides (A = adenine, T = thymine, C = cytosine, and G = guanine). Your DNA lives inside every cell of your body, broadly functioning like a recipe book listing the ingredients and methods to make you.
The recipe book is broken down into 46 chapters called chromosomes, half of which came from your mother, and half from your father. When you lay your chromosomes out in pairs, you get your karyotype.
Different species have different numbers of chromosomes. For instance, rats have 42 chromosomes making up their DNA. Chickens have 78 chromosomes. And butterflies have really run away with the idea, evolving 380 chromosomes per individual.
The number of chromosomes isn't down to an organism's complexity—but rather random chromosome mutation.
Back to the DNA recipe book: if chromosomes are like chapters, then genes are like individual recipes.
Rarely, your physical traits are determined by a single-gene recipe with multiple variants (called alleles). For instance, there is only one gene involved in producing eye colour, but six different alleles (brown, blue, grey, green, hazel, amber, and red).
However, most of your traits are the result of multiple gene interactions, also with multiple alleles. Examples include intelligence, autism, or coat colour if you happen to be a Golden Retriever.
It's pretty complex business, which is why we have so far to go in analysing the human genome.
When we say that your DNA is 99% similar to a chimpanzee, we're comparing the genes between two species. Yet when we say you have 50% of DNA in common with your sibling, it's a much more specific comparison of alleles.
We'll look at how genes are expressed in a moment. But first, let's take a look at how genes, chromosomes, and DNA relate to each other in real life.
Genes vs Chromosomes
Genes are long stretches of nucleotides that make up chromosomes, averaging 27,000 bases long in humans. There are several thousand genes bundled into each chromosome.
This bundling and coiling of DNA is a finely tuned process, with different coiling styles happening in different cell types relevant to local gene expression.
In other words, while every cell in your body contains the genes that produce eye colour, these genes are coiled on the outside of chromosomes in your iris cells. They're much more accessible where needed.
Your chromosomes coil and uncoil all the time. When a cell divides, for example, all 46 chromosomes unravel into vast stretches of DNA. This exposes the base pairs to be copied, before they re-coil into their resting chromosome state.
The Molecular Structure of DNA
From now on, we're going to zoom in and look at how DNA works very closely indeed.
The double helix shape of DNA was intuited by Watson and Crick in 1953. However, few people know that this discovery was dependent on many other scientists before them, including Rosalind Franklin's X-ray crystallography photos which provided the critical clue to its structure.
We can think of DNA as a molecular jigsaw puzzle. Except there are only six different shapes and 18 billion pieces overall.
The six shapes in question are the DNA nucleotides (adenine, thymine, guanine, and cytosine) and the DNA backbone (sugar rings and phosphate groups).
Due to their molecular shapes, adenine always binds with thymine, while guanine always binds with cytosine. Meanwhile, chemical properties compel the bases and backbone to join together like a ladder, producing order out of apparent molecular chaos.
In The Mysterious World of The Human Genome, Frank Ryan gives us an analogy of the molecular structure of DNA. Imagine you're standing on a train track that stretches out to the horizon. The vertical rails represent the backbone of DNA, while the sleepers represent the nucleotide pairs.
The train track is very long. If you walked along it, you could count off billions of sleepers. Your entire genome—that's the sequence of all your DNA combined—is three billion nucleotides long.
The sequence of nucleotides provides the instructions to make proteins: the basis of all living tissues. Proteins are also key to biological processes; catalysing reactions, transporting molecules, and sending chemical signals around the body.
When the entire human genome was successfully sequenced in 2003, only 2% was found to comprise coding DNA for making proteins. The other 98% comprises non-coding DNA.
Some stretches of non-coding DNA have since been identified as regulatory DNA, providing rule sets on how to replicate. Other stretches have been identified as viral DNA, inserted into the genome after exposure to viruses.
The vast remainder is still largely a mystery. We have the sequence of many individual humans—but we still don't know what most of it does. Even the precise number of genes in human DNA remains elusive.
How Are Genes Expressed?
Now we have the structure, how does DNA physically produce your body? If DNA is like a recipe book, how are the ingredients put together?
This is known as gene expression, and it's happening all the time in your body to produce life-sustaining proteins on demand. DNA isn't just a blueprint for foetal growth; it's essential for day-to-day survival, such as making insulin if you've just had breakfast, or cortisol to regulate your stress response.
In this way, your DNA continually responds to your environment. Sometimes, genes can be switched on or off en masse—sometimes permanently—which gives you a unique epigenetic profile shaped by your physical, mental, and emotional environment.
Gene expression takes place in three stages, known as the Central Dogma. This is the real guts of how DNA works.
- Transcription makes a copy of the gene recipe
- RNA Processing customises the gene recipe
- Translation converts the gene into a product
Let's look at this fascinating molecular dance in more detail.
Step 1. DNA is Transcribed into RNA
During transcription, the double helix DNA unwinds to expose the genes to be expressed. It then makes a single-stranded copy of the DNA, known as RNA. This keeps the original DNA blueprint safe out of the kitchen, so the the cooks can't accidentally spill bolognaise sauce on it.
In transcription, a molecule known as RNA polymerase travels along the DNA helix, teasing apart the two strands. This exposes one side of the DNA ladder, so it can be rebuilt with free-floating nucleosides (a nucleoside is a nucleotide attached to a sugar ring).
The new string is then teased apart to create a single-stranded RNA molecule. The original DNA then heals up and re-coils for next time.
Now we have a photocopy of the gene recipe we want to use. What next?
Step 2. RNA is Processed and Modified
During RNA processing the new strand of RNA goes through some important modifications. First, a cap and tail are added, determining how long the gene should be expressed. We're now measuring out the ingredients.
Next up, spliceosomes step in to remove non-coding stretches of nucleotides, called introns. This leaves behind only coding stretches, called exons. The easy way to remember this is that exons exit the nucleus here to be expressed.
Next, some really breathtaking complexity emerges. Alternative splicing pastes different stretches of nucleotides together to produce different end-products.
Step 3. RNA is Translated into Amino Acids
The third stage of gene expression is called translation because there is a change of language: from nucleotides to amino acids.
A molecular complex called a ribosome moves along the RNA strand, handling three nucleotides at a time. Each set of three nucleotides is called a codon.
The codons are matched to free-floating molecules called transfer RNA, which carry complimentary anti-codons and their corresponding amino acids. It's a repetitive matching process that gives rise to chains of amino acids.
The result of translation is a long chain of amino acids, known as a polypeptide. Polypeptides then amass and fold into specific functional shapes to make proteins.
Success! Your DNA has been converted safely into proteins to perform life-sustaining work in the body. We're talking testosterone, melatonin, lactase, collagen, and many, many more. In fact, no-one knows how many types of proteins there are in the human proteome. Estimates range from 10,000 to several billion.
The Genetic Code
"Tell me more about the codons!" I hear you scream. And you'd be right. This is a good thing to scream about, if anything is.
The relationship between codons and amino acids is defined by the genetic code, which is universal to all life on Earth. For instance, the nucleotide sequence C-G-C translates to the amino acid arginine, while A-U-G translates to methionine. Note that in the process of transcribing DNA into RNA, thymine was switched out for a very similar molecule called uracil.
Here is nature's complete genetic code:
The genetic code provides us with fascinating insights into evolution. There are 64 possible codons in all (4 x 4 x 4) and only 20 amino acids. This means multiple codons translate to the same amino acid, creating redundancy in the genetic code.
However, this is generally a good thing. It dampens the effects of mutations that cause catastrophic disease. A mutation from G-U-U to G-U-C still produces valine, bypassing a valine deficiency that would otherwise cause neurological defects.
There are other repercussions to having redundancy in the genetic code. See my article, Evolution Explained, to learn more about positive, negative, and neutral mutations. To learn about gene replacement therapy to correct inherited diseases, see How Does Gene Therapy Work?
How Fast Does DNA Work?
Your DNA is translated at an astonishing rate. A single ribosome can produce dozens of polypeptide chains every second. And there are 10 million ribosomes at work in a typical cell, allowing it to throw out massive numbers of protein molecules alongside thousands of sister cells.
It's all rather astonishing really. DNA and its entourage perform a continual complex choreography, culminating in the normal functioning of any living organism, such as a friendly newt or toad. Isn't that brilliant?